Cyclophosphamide (also known as cytoxan) is one of the most widely used anti-cancer drugs in the world. It is administered in combination with a number of other drugs to treat a wide variety of hematologic and solid tumors. However, there are several features of the drug that can detract from its clinical efficacy. First, the drug requires metabolic activation in the liver to produce metabolites that are toxic to cancer cells. Second, the drug is specifically toxic to the urinary bladder and also displays the bone marrow toxicity typical of the alkylating agent class of anti-cancer drugs. Third, cyclophosphamide is a potent suppressor of the immune system at the doses used to treat cancer, thus decreasing the infection-fighting ability of patients already debilitated by their disease. Finally, repeated use of cyclophosphamide frequently results in the development of resistance to the drug in a patient's cancer cells, thus rendering the drug ineffective.
The present invention describes new cyclophosphamide compounds that will circumvent one or more of these problems. The compounds of the present invention are effective in treating tumors in animals that have developed resistance to cyclophosphamide itself. These compounds are free of the urinary bladder toxicity exhibited by cyclophosphamide. Finally, compounds included within the present invention do not require metabolism in the liver to acquire anti-tumor activity.